| Title: | A systematic analysis of the contribution of genetics to multimorbidity and comparisons with primary care data |
| Journal: | EBioMedicine |
| Published: | 6 Feb 2025 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/39919332/ |
| DOI: | https://doi.org/10.1016/j.ebiom.2025.105584 |
Publication 14427
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Abstract
BACKGROUND: Multimorbidity, the presence of two or more conditions in one person, is common but studies are often limited to observational data and single datasets. We address this gap by integrating large-scale primary-care and genetic data from multiple studies to interrogate multimorbidity patterns and producing digital resources to support future research.</p>
METHODS: We defined chronic, common, and heritable conditions in individuals aged ≥65 years, using two large primary-care databases [CPRD (UK) N = 2,425,014 and SIDIAP (Spain) N = 1,053,640], and estimated heritability using the same definitions in UK Biobank (N = 451,197). We used logistic regression to estimate the co-occurrence of pairs of conditions in the primary care data. Linkage disequilibrium score regression was used to estimate genetic similarity between pairs of conditions. Meta-analyses were conducted across databases, and up to three sources of genetic data, for each pair of conditions. We classified pairs of conditions as across or within-domain based on the international classification of disease.</p>
FINDINGS: We identified 72 chronic conditions, with 43.6% of 2546 pairs showing higher co-occurrence than chance in primary care and evidence of shared genetics. Many across-domain pairs exhibited substantial shared genetics (e.g., iron deficiency anaemia and peripheral arterial disease: genetic correlation Rg = 0.45 [95% Confidence Intervals 0.27:0.64]). 33 pairs displayed negative genetic correlations, such as skin cancer and rheumatoid arthritis (Rg = -0.14 [-0.21:-0.06]), due to potential adverse drug effects. Discordance between genetic and primary care data was also observed, e.g., abdominal aortic aneurysm and bladder cancer co-occurred in primary care but were not genetically correlated (Odds-Ratio = 2.23 [2.09:2.37], Rg = 0.04 [-0.20:0.28]) and schizophrenia and fibromyalgia were less likely to co-occur together in primary care but were positively genetically correlated (OR = 0.84 [0.75:0.94], Rg = 0.20 [0.11:0.29]).</p>
INTERPRETATION: Most pairs of chronic conditions show evidence of shared genetics, and co-occurrence in primary care, suggesting shared mechanisms. The identified patterns of shared genetics, negative correlations and discordance between genetic and observational data provide a foundation for future multimorbidity research.</p>
FUNDING: UK Medical Research Council [MR/W014548/1].</p>
25 Authors
- Olivia Murrin
- Ninon Mounier
- Bethany Voller
- Linus Tata
- Carlos Gallego-Moll
- Albert Roso-Llorach
- Lucía A. Carrasco-Ribelles
- Chris Fox
- Louise M. Allan
- Ruby M. Woodward
- Xiaoran Liang
- Jose M. Valderas
- Sara M. Khalid
- Frank Dudbridge
- Sally E. Lamb
- Mary Mancini
- Leon Farmer
- Kate Boddy
- Jack Bowden
- David Melzer
- Timothy M. Frayling
- Jane A.H. Masoli
- Luke C. Pilling
- Concepción Violán
- João Delgado
1 Application
| Application ID | Title |
|---|---|
| 9072 | The Genetics of anthropometric traits ? Height, weight, BMI and waist circumference |
Enabling scientific discoveries that improve human health